U.S. Pat. No. 6,004,528, incorporated herein by reference, discloses that cancer lesions contain a small but highly virulent sub-population of abnormal stem cells and that these “cancer stem cells” play a significant role in the malignancy of the cancer and in the resistance of the cancer to many standard therapies. Cancer stem cells have been identified, for example, in acute myeloid leukemia (Jordan, C. T., et al (2000) Leukemia 14, 1777-1784), chronic myeloid leukemia (Jamieson, C. H. M., et al (2004) N Engl J Med 351, 657-667), breast cancer (Al-Hajj, M. et al (2003) Proc. Natl. Acad. Sci. USA 100, 3983-3988), brain cancer (Singh, S. K. et al (2003) Cancer Res 63, 5821-5828), multiple myeloma (Matsui, W., et al (2004) Blood 103, 2332-2336), and other cancer types.
The presence of cancer stem cells may lead to recurrences of cancer after treatment. To prevent recurrences, cancer therapies need to eliminate cancer stem cells (Reya T., et al (2001) Nature 414, 105-111).
Stem cells in any tissue, whether normal or malignant, are present in very small numbers and they are difficult to identify and even more difficult to isolate. There is a pressing need for methods to identify and isolate cancer stem cells so that their gene expression profiles, potential drug targets, and properties may be characterized, including their sensitivity to various anti-cancer therapeutic agents and new agents identified through rational drug design or drug screens.
The present invention addresses these and other needs in the art by providing methods for identifying cancer stem cell genes and gene products, i.e., targets, which in turn provide tools for drug discovery, and molecules that identify a cancer cell as a cancer stem cell, e.g., for targeting antibodies. The invention also provides assay systems for discovering or evaluating anti-cancer stem cell-based cancer therapeutics.